Metadynamics to Enhance Sampling in Biomolecular Simulations.

Abstract

Molecular dynamics is a powerful simulation method to provide detailed atomic-scale insight into a range of biological processes including protein folding, biochemical reactions, ligand binding, and many others. Over the last several decades, enhanced sampling methods have been developed to address the large separation in time scales between a molecular dynamics simulation (usually microseconds or shorter) and the time scales of biological processes (often orders of magnitude longer). This chapter specifically focuses on the metadynamics family of methods, which achieves enhanced sampling through the introduction of a history-dependent bias potential that is based on one or more slow degrees of freedom, called collective variables. We introduce the method and its recent variants related to biomolecular studies and then discuss frontier areas of the method. A large part of this chapter is devoted to helping new users of the method understand how to choose metadynamics parameters properly and apply the method to their system of interest.